Recurrent circadian circuitry regulates central brain activity to maintain sleep

Neuron. 2022 Jul 6;110(13):2139-2154.e5. doi: 10.1016/j.neuron.2022.04.010. Epub 2022 May 6.


Animal brains have discrete circadian neurons, but little is known about how they are coordinated to influence and maintain sleep. Here, through a systematic optogenetic screening, we identified a subtype of uncharacterized circadian DN3 neurons that is strongly sleep promoting in Drosophila. These anterior-projecting DN3s (APDN3s) receive signals from DN1 circadian neurons and then output to newly identified noncircadian "claw" neurons (CLs). CLs have a daily Ca2+ cycle, which peaks at night and correlates with DN1 and DN3 Ca2+ cycles. The CLs feedback onto a subset of DN1s to form a positive recurrent loop that maintains sleep. Using trans-synaptic photoactivatable green fluorescent protein (PA-GFP) tracing and functional in vivo imaging, we demonstrated that the CLs drive sleep by interacting with and releasing acetylcholine onto the mushroom body γ lobe. Taken together, the data identify a novel self-reinforcing loop within the circadian network and a new sleep-promoting neuropile that are both essential for maintaining normal sleep.

Keywords: calcium imaging; circadian rhythm; neural circuits; optogenetics; sleep.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / physiology
  • Circadian Rhythm / physiology
  • Drosophila / metabolism
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster* / physiology
  • Sleep / physiology


  • Drosophila Proteins